Our group has demonstrated that the nonlinearly generated, subharmonic signal component from microbubble-based ultrasound contrast agents is an excellent indicator of the hydrostatic pressure variation (from 20 to 200 mmHg). Based on such results, a technique called SubHarmonic-Aided Pressure Estimation (SHAPE) has been proposed. SHAPE has the potential to noninvasively measure changes in pressure. It estimates internal pressure variations by transmitting at one frequency but receiving only at its subharmonic frequency. The fundamental hypothesis of this project is that ambient blood pressure can be monitored and quantified noninvasively using SHAPE. Thus, essential information regarding the functional integrity of the cardiovascular system can be provided noninvasively. Initial experiments will be conducted in vitro to test the effects of hydrostatic pressure on the subharmonic performance of ultrasound contrast agents in order to select the best agent for SHAPE. These efforts will be supported by a computer simulation study of SHAPE. Next, the SHAPE algorithm will be implemented on a state-of-the-art ultrasound scanner (Logiq 9, GE Healthcare, Milwaukee, Wl) for real time pressure measurements. The in vivo SHAPE results will be calibrated based on manometer-tipped catheter (i.e., pressure transducer) measurements in the inferior vena cava (IVC) of 5 canines. Following the calibration studies, in vivo pharmacologically induced pressure changes in the aorta (selected to investigate higher pressure variations) will be studied (in 10 dogs) using SHAPE and results compared to catheter based pressure measurements. Finally, two groups of 10 dogs with portal hypertension (induced by embolization or by a surgically created arterio-venous fistula) will be studied with SHAPE comparing results to catheter based pressure measurements. In conclusion, this study aims to develop a novel and innovative ultrasound based method (i.e., SHAPE) for noninvasive evaluation of blood pressure and portal hypertension in vivo. Currently there are no accurate, methods available to measure the pressure in blood vessels deep in the body. This grant will develop such a technique by monitoring the behavior of very small, gas bubbles within the blood using ultrasound. This will allow potentially life-threatening diseases, such as increased pressure in the liver, to be diagnosed early. [unreadable] [unreadable] [unreadable]